This proposal for research has several objectives which are associated with the structure, function and biosynthesis of the circulatory glycoproteins. The structure of the carbohydrate of the blood-clotting glycoprotein, prothrombin, will be investigated as well as other blood-clotting glycoproteins. Unusual structures have been identified in the carbohydrate of prothrombin and blood-clotting factor X which include the presence of alpha-galactoside residues in prothrombin and galactosamine in factor X. The possibility that these structures are performing an important role in some aspect of blood-coagulation could be a primary contribution of this work. The physiological significance of the rapid removal of the activation products of prothrombin from the circulation will be studied. It is proposed that this system may be necessary to maintan proper blood-clotting potential (since these activation products inhibit the blood-clotting reactions) or it may be a general system which identifies and removes denatured or modified proteins from the circulation system. The biosynthesis of the carbohydrate of the circulatory glycoproteins will be studied by administration of modified carbohydrate precursors and by examining the effects of these compounds on the properties of the circulatory glycoproteins. These studies will primarily involve sialic acid and the role of the various forms of sialic acid found in nature. The potential effect of cyclic-AMP on sialic acid biosynthesis will also be determined. The presence of the vitamin K-dependent amino acid, gamma-carboxyglutamate, in proteins and extracts will be investigated in an attempt to determine the distribution of this amino acid in nature.